1. Field of the Invention
This invention relates to the in vivo treatment of tumors and more particularly to treating tumors by removing immunoglobulins and immune complexes from the blood of patients afflicted with malignant tumors. The invention also relates to apparatus for removing these immunoglobulins and immune complexes.
2. Description of the Prior Art
In patients with cancer, it is known that there are soluble immunosuppressive substances in the blood serum which interfere with the ability of the leukocytes to attack and destroy the tumor cells. These "blocking factors" seem to develop in the early stages of tumor growth and have been demonstrated to be present in sera of animals and humans with growing tumors. It has also been found that Protein A (SpA), which is found in the cell wall of Staphylococcus aureus can absorb these "blocking factors" from the sera of animals and patients bearing actively growing tumors. The use of killed S. aureus containing Protein A in order to remove immunoglobulins containing blocking activity from the blood of cancer patients for therapeutic purposes was suggested by G. Steele, Jr. et al, Int. T. Cancer 15:180, 1975. Treatment of tumors in cancer patients by immunoadsorption of proteins from their blood serum by contacting the serum with immobilized Protein A has been reported by Bansal, S. C., et al, Cancer 1978, Vol. 42 pp. 1-18; Terman, D. S., et al, New England Journal of Medicine 1981, Vol. 305, pp. 1195-1200; Ray, P. K., et al., Cancer 1982, Vol. 49, pp. 1800-1809; and Bensinger, W. I., International Cancer Meeting Abstracts, Seattle, September 1982. In these treatments, blood was continuously withdrawn from the patient, the cellular components were separated from the serum, the serum was passed over immobilized Protein A, the serum was recombined with the cells and the blood was reinfused.
The methods of immobilizing the Protein A in these treatments included using killed S. aureus having Protein A as a constituent of the cell wall, immobilizing the Protein A in a matrix of charcoal and collodion, and covalently binding the Protein A to the surface of crystalline silica. In each case the immunoadsorption treatment was apparently conducted with the immunoadsorbent at room temperature.
In each case some regession of the tumors in at least some of the patients treated was reported. However, in each case the treatments were also accompanied by side effects such as fever, chills, hypotension, tachycardia and bronchospasm. In some instances, therapeutic intervention was required to control these side effects.
Hence, a need has continued to exist for a method of removing cytotoxicity-inhibiting substances from the blood serum of cancer patients which avoids the side effects of the known procedures.